Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: the INSPIRE Study
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ORIGINAL RESEARCH published: 17 April 2019 doi: 10.3389/fnut.2019.00045 What’s Normal? Microbiomes in Human Milk and Infant Feces Are Related to Each Other but Vary Geographically: The INSPIRE Study Kimberly A. Lackey 1, Janet E. Williams 2, Courtney L. Meehan 3, Jessica A. Zachek 2, Elizabeth D. Benda 2, William J. Price 4, James A. Foster 5, Daniel W. Sellen 6, Elizabeth W. Kamau-Mbuthia 7, Egidioh W. Kamundia 7, Samwel Mbugua 7, Sophie E. Moore 8,9, Andrew M. Prentice 10, Debela Gindola K. 11, Linda J. Kvist 12, Gloria E. Otoo 13, Cristina García-Carral 14, Esther Jiménez 14, Lorena Ruiz 15, Edited by: Juan M. Rodríguez 16, Rossina G. Pareja 17, Lars Bode 18,19, Mark A. McGuire 2 and Aldo Corsetti, Michelle K. McGuire 1* University of Teramo, Italy 1 Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States, 2 Department of Reviewed by: Animal and Veterinary Science, University of Idaho, Moscow, ID, United States, 3 Department of Anthropology, Washington Arianna Aceti, State University, Pullman, WA, United States, 4 Statistical Programs, College of Agricultural and Life Sciences, University of University of Bologna, Italy Idaho, Moscow, ID, United States, 5 Department of Biological Sciences, University of Idaho, Moscow, ID, United States, Veronique Demers-Mathieu, 6 Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada, 7 Department of Human Nutrition, Egerton Oregon State University, United States University, Nakuru, Kenya, 8 Department of Women and Children’s Health, King’s College London, London, United Kingdom, *Correspondence: 9 MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, Gambia, 10 MRC International Michelle K. McGuire Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom, 11 Department of Anthropology, [email protected] Hawassa University, Hawassa, Ethiopia, 12 Faculty of Medicine, Lund University, Lund, Sweden, 13 Department of Nutrition and Food Science, University of Ghana, Accra, Ghana, 14 Probisearch, Tres Cantos, Spain, 15 Department of Microbiology Specialty section: and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Spain, This article was submitted to 16 Department of Nutrition, Food Science, and Food Technology, Complutense University of Madrid, Madrid, Spain, Food Microbiology, 17 Nutrition Research Institute, Lima, Peru, 18 Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research a section of the journal Excellence, University of California, San Diego, La Jolla, CA, United States, 19 Department of Pediatrics, University of Frontiers in Nutrition California, San Diego, La Jolla, CA, United States Received: 20 December 2018 Accepted: 27 March 2019 Background: Microbial communities in human milk and those in feces from breastfed Published: 17 April 2019 infants vary within and across populations. However, few researchers have conducted Citation: Lackey KA, Williams JE, Meehan CL, cross-cultural comparisons between populations, and little is known about whether Zachek JA, Benda ED, Price WJ, certain “core” taxa occur normally within or between populations and whether variation Foster JA, Sellen DW, in milk microbiome is related to variation in infant fecal microbiome. The purpose of this Kamau-Mbuthia EW, Kamundia EW, Mbugua S, Moore SE, Prentice AM, study was to describe microbiomes of milk produced by relatively healthy women living at K. DG, Kvist LJ, Otoo GE, diverse international sites and compare these to the fecal microbiomes of their relatively García-Carral C, Jiménez E, Ruiz L, Rodríguez JM, Pareja RG, Bode L, healthy infants. McGuire MA and McGuire MK (2019) Methods: We analyzed milk (n = 394) and infant feces (n = 377) collected from What’s Normal? Microbiomes in Human Milk and Infant Feces Are mother/infant dyads living in 11 international sites (2 each in Ethiopia, The Gambia, Related to Each Other but Vary and the US; 1 each in Ghana, Kenya, Peru, Spain, and Sweden). The V1-V3 region Geographically: The INSPIRE Study. Front. Nutr. 6:45. of the bacterial 16S rRNA gene was sequenced to characterize and compare microbial doi: 10.3389/fnut.2019.00045 communities within and among cohorts. Frontiers in Nutrition | www.frontiersin.org 1 April 2019 | Volume 6 | Article 45 Lackey et al. The INSPIRE Study Results: Core genera in feces were Streptococcus, Escherichia/Shigella, and Veillonella, and in milk were Streptococcus and Staphylococcus, although substantial variability existed within and across cohorts. For instance, relative abundance of Lactobacillus was highest in feces from rural Ethiopia and The Gambia, and lowest in feces from Peru, Spain, Sweden, and the US; Rhizobium was relatively more abundant in milk produced by women in rural Ethiopia than all other cohorts. Bacterial diversity also varied among cohorts. For example, Shannon diversity was higher in feces from Kenya than Ghana and US-California, and higher in rural Ethiopian than Ghana, Peru, Spain, Sweden, and US-California. There were limited associations between individual genera in milk and feces, but community-level analyses suggest strong, positive associations between the complex communities in these sample types. Conclusions: Our data provide additional evidence of within- and among-population differences in milk and infant fecal bacterial community membership and diversity and support for a relationship between the bacterial communities in milk and those of the recipient infant’s feces. Additional research is needed to understand environmental, behavioral, and genetic factors driving this variation and association, as well as its significance for acute and chronic maternal and infant health. Keywords: human milk, breastmilk, feces, microbiome, international, infant, breastfeeding, maternal INTRODUCTION by women living in Finland (n = 18), while Davé et al. (9) reported Streptococcus, Staphylococcus, Xanthomonadaceae, Although long thought to be sterile, human milk is now known and Sediminibacterium were the most abundant taxa in milk to contain myriad bacteria, and growing evidence suggests produced by Mexican-American mothers (n = 10). In Chinese that the composition and profiles of these microbiomes differ and Taiwanese women (n = 133), family-level analysis revealed among geographically distinct populations of women. The Streptococcaceae, Pseudomonadaceae, Staphylococcaceae, microbiome of milk produced by healthy women is of scientific Lactobacillaceae, and Oxalobacteraceae as the most abundant and public health interest because these microbes may, at least taxa (10). Other reports suggest additional differences among in part, determine which microbial communities are in the populations (11–16), although some similarities are notable, gastrointestinal (GI) tracts of their infants (1–5). The infant GI such as the dominance of members of the Streptococcaceae microbiome (often assessed through the analysis of feces) is of and Staphylococcaceae families. It is unknown, however, if this substantial interest because its variation has been associated with variation is due to genuine differences among populations, a variety of human diseases, both in early and later life [reviewed differences in location of milk collection (e.g., hospital vs. home), in (6)]. or differences in sample collection methods, storage, processing, In the first report of a complex bacterial community in human and analyses. This is a persistent problem in microbiome research milk using high-throughput methodology, the milk microbiome and can only be solved with rigorously controlled studies of of healthy women (n = 16) in the Moscow, ID/Pullman, WA representative cohorts of women from diverse populations, region of the United States was found to be dominated by including standardized milk collection protocols. Streptococcus, Staphylococcus, Serratia, and Corynebacterium To this end and to help address other potential confounders, (7). Bacterial communities appeared to be somewhat unique Kumar et al. (17) investigated the influence of geographic for each woman, although 9 “core” genera were common all location on the milk microbiome by collecting and analyzing samples. Since the publication of this paper, additional studies milk produced by 80 healthy women (20 each from Spain, have suggested that the primary bacterial taxa in milk vary Finland, South Africa, and China) at 1 mo postpartum. across populations (Supplementary Table 1). For example, Substantial differences were found among cohorts, and variation Cabrera-Rubio et al. (8) found that Leuconostoc, Weisella, and was related to a variety of factors, such as delivery mode. For Lactococcus were the most predominant genera in milk produced example, milk produced by Chinese women contained relatively more Streptococcus than milk produced by women in all other Abbreviations: ANOSIM, analysis of similarity; ANOVA, analysis of variance; GI, cohorts, while milk produced by Spanish women had relatively gastrointestinal; GLIMMIX, generalized linear mixed model; HMO, human milk more Propionibacterium and Pseudomonas than that produced in oligosaccharide; ASV, amplicon sequence variants; ETR, Ethiopia, rural site; ETU, other locations. This study also demonstrated that milk produced Ethiopia, urban site; GBR, The Gambia, rural site; GBU, The Gambia, urban site; GN, Ghana; KE, Kenya; PE, Peru; SP, Spain; SW, Sweden; USC, United States, by Spanish and South African women was characterized by California site; USW,